Why The World’s First Drugs Ate Your Butt Cheeks and Turned You Blue
HTML-код
- Опубликовано: 10 июл 2024
- 💉 Whether we like it or not, drugs are a fundamental part of our modern world. But what were "early drugs" like, back in the day? At some point, we clearly moved from drilling holes in people's skulls, to using synthetic molecules as medicines. In this video, we will walk through the history, science and chemistry of some of the early advances.
If you want to fully appreciate the content of upcoming videos on (shocking) history of cancer treatments and modern chemotherapies, you should pay attention!
00:00 Early drugs were CRAZY
00:36 Dubious ancient methods: Mummies?!
01:43 Paul Ehrlich: Stains paving the way of discovery
02:59 Advent of chemotherapy and magic bullets: Methylene blue
03:36 Synthesis of methylene blue
06:45 Malaria in a nutshell, and use of methylene blue
08:29 Mechanism of action of methylene blue
10:27 Provay Blue for treatment of methemoglobinemia
11:33 Methylene blue for treatment of malaria today
12:45 Ehrlich's work in immunology and syphilis
14:07 Mercury and arsenic as medicine?!
16:10 The birth of medicinal chemistry: Salvarsan/ arsphenamine
17:25 Translation of Salvarsan from clinic to market
18:32 Necrosis and arsenic deposits in butt cheeks
19:15 Chemistry insight #1: Neosalvarsan
19:54 Chemistry insight #2: Synthesis of salvarsan and impurities
21:21 Chemistry insight #3: Salvarsan structure
22:46 Conclusions and THANKS!
/ totalsynthesis
🚀 Thanks to all channel supporters!!!
/ totalsynthesis_official
👉 Follow me on IG to learn about interesting news and mechanism quizzes!
www.total-synthesis.com
Disclaimer - This channel does not provide medical advice!
No information on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of information on RUclips.
Key references:
- ISIS. 1985, 76, 319: Ancient and medieval chemotherapy for cancer
- Beiträge zur Theorie und Praxis der histologischen Färbung; P. Ehrlich, Leipzig, 1878 (www.pei.de/DE/institut/paul-e...)
- Biologisches Zentralblatt 1887, 6, 214 | Ueber die Methylenblaureaktion der lebenden Nervensubstanz
- Berlin Klin Woch 1891, 28, 953 | Ueber die Wirkung des Methylenblau bei Malaria.
- Malaria Journal 2016, 15, 51 | Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites
- Lancet Infectious Diseases 2018, 18, 627 | Efficacy and safety of primaquine and methylene blue for prevention of Plasmodium falciparum transmission in Mali: a phase 2, single-blind, randomised controlled trial
- Berlin Klin Woch 1899, 36, 481
- Proc. R. Soc. Lond. B. 1905, 76, 589 | The experimental treatment of trypanosomiasis in animals
- Annales de chimie et de physique 1854, 42, 186 | Sur la nitronaphtaline et la nitrobenzine
- Bull. Hist. Chem. 1999, 23, 28 | Places and chemistry: Strasbourg - A chemical crucible seen through historical personalities
- Wechselmann: The Treatment of Syphilis with Salvarsan (1911), New York: Rebman, 11
- J r Soc Med 2009, 102, 343 | The introduction of 'chemotherapy' using arsphenamine - the first magic bullet
- Ber. Dtsch. Chem. Ges. 1912, 45, 756 | Über das salzsaure 3.3′-Diamino-4.4′-dioxy-arsenobenzol und seine nächsten Verwandten
- JACS 1920, 42, 2402 | HYPOPHOSPHOROUS ACID PREPARATION OF ARSPHENAMINE. (3,3-DIAMINO-4,4-DIHYDROXY-ARSENO-BENZENE DIHYDROCHLORIDE)
- ACIE 2005, 44, 829 | The composition of Ehrlich's salvarsan: resolution of a century-old debate 
Наука
Please let me know how you liked this video!
Thanks for watching and a special shoutout to the channel members!
www.patreon.com/totalsynthesis; instagram.com/totalsynthesis_official/
Have you or will you [if not already] maybe look into doing a video on ephedrine and pseudoephedrine and its history and chemistry, [bio]synthetic production routes and particularly the specific need of [discovery] synthesis in even making it/them comercially or otherwise available, since plant & otherwise extraction provided only a bare minimum of it, even on largest of scales. Good opportunity also to explain stereochemistry and enantiomers *shrugs*. If nothing else a very interesting thread of the same brand/flavor of [chem] history your content aligns with and/or [seems to] favor or prefer
@@Conscious_Creator_Era I have had this on my long list of future videos for some time - think it's a nice topic! Thanks for recommending and let's see if I ever get to it over some of the other things :)
"Ancient persian medicine used asphalt to treat wounds" - we still do that today, just a tad more refined. It's called Ichthammol or the "ammonium salt of sulfonated shale oil". Can be bought as an ointment with up to 50% concentration, has anti-inflammatory, pain relieving and bactericidal effects (without known resistances) and additionally helps abscesses with draining and the body expelling foreign objects. I use the stuff whenever I have an ingrown toe nail or a splinter I can't get out. Gets rid off the problem within 3 days.
Nice
Carcinogenic, though. That's why it was taken out of open trade and transferred to the prescription only category, here in the Netherlands.
So you might want to refrain from using it for every little booboo.
Personally, I would only use the tar ointment to help the abscess pop. When it's open, I'd switch to honey.
@@remcovanvliet3018 It's still available OTC in Austria and Germany, so the Netherlands restricting it was a national solo endeavour instead of something enforced by EMA. Also, the substance is water soluble, doesnt intercalate DNA and cant cross human cell membranes, all of which make definite and proven carcinogenicity seem rather unlikely. It may be a "possible carcinogen" like Glyphosate where it's neither proven, nor disproven.
I wonder if vaseline is another modern incarnation of the same concept. Well known to support healing of small wounds.
@@FUZxxl AFAIK the positive effects of vaseline result from keeping the tissue moist and elastic while at the same time preventing/reducing scab formation.
Good old methylene blue! Not only does it work great in the blue bottle experiment (along with indigo carmine and resazurin) but some people use it as a nootropic to this day...
Thanks for mentioning this. I dove into the PubMed rabbit hole regarding this substance and now I'll have a lot to talk about with my collegues tomorrow.
@@Psychx_ "Protection against neurodegeneration with low-dose methylene blue and near-infrared light"
Lololol. I watched a show once. Pretty sure they made a "nootropic" with methylene 😅
I do. Can't tell if it's helping yet but I'm going to keep using it for the foreseeable future.
Ah, methylene blue, what a fantastic molecule. Did you know that it was also the first drug used in psychiatry? Apparently, it reduced psychotic symptoms and helped with depression
It’s better than SSRIs. It just might require diet restrictions. It’s a MAOI
Yeah that molecule is pretty wild, also useful for some organic syntheses
@@2010RSHACKSI don't necessarily agree with you, but everyone has different reactions to different antidepressants, MAOIs can be great for people, who did not benefit from SSRIs. Although SSRIs are waaay safer, more common and I think more effective.
If taking, need to stop ssri drugs and st John's wort to prevent serotonin sndrome
Anyone know if it actually helps schizophrenia?
They also treated the blue people from kentucky with methylene blue. The suffered from methemoglobinemia due their genetic heritage. Thats why they had blue skin. The treatment was peotic: blue people took blue pills went from smurf to normal human colour and pissed the blue out (residue of methylene blue in urine)
Was that one treatment, or did they have to take it, their entire lives?
@@TwisterTornado they had to take it for their lives, because the enzym which converts Fe3+ to Fe2+ is not working. Another treatment could be ascorbic acid, which also reduces the iron.
there is a nice article on this, but youtube is alway deleting my links "Owlcation: Blue People of Kentucky: Why the Fugate Family Had Blue Skin"
"A simple injection of the dye caused a stunning color change. Within minutes, Patrick changed from blue to pink. This, however, was a temporary fix. The dye couldn't fix their enzyme deficiency, so Dr. Cawein left the people with a supply of methylene blue pills to be taken on a continual basis."
Most likely periodically because they will keep making methemoglobin. They lack an enzyme whic reduces the oxidized form of iron (fertic?) hemoglobin. The oxidized form is bluish, and the hemoglobin with it does not carry oxygenas well as the ferrous.
That is a banger of a title lmao
😂 I hope the algo agrees!
@@totalsynthesisyour in your way to a milly
"you could probably predict the process"
Me, trying to remember high school chemistry: "sure pal"
😂
Thanks for such thorough and succinct coverage of these topics. It’s always a good day when total synthesis uploads🔥
Thanks mate, much appreciated! 💕
Im so glad you made a video on methylene blue, I've been taking it every now and then for around a month now, not because I believe it is of any use, I just get a kick out of it.
Cheers.
As not a chemist, I enjoyed this video bit more than nuts and bolts of modern synthesis methods, that goes over my head. Added madness of early medicine is cherry on top.
Great to hear! I tried to pepper in some broader info rather than just chemistry (in part also because early chemistry is not massively interesting or complex). So I'm happy you enjoyed it!
Methylene Blue when taken orally does no such thing, this is also the first time I've seen these kinds of statements against the injected form.
Holy shit, that picture with 64% methemoglobinemia patient with cyanotic tongue looked remarkably like a corpse.
To be fair some ancient medicines/treatments do work okay, especially if they don't have devastating side effects.
Even those can be unsafe if misused by careless or ignorant people though.
Nice work, as always ^^
Thank you!!
Thanks,this fills in the gap in my knowledge on why we test our chemicals with color. Algarsamy didn't make it clear to me. Could you do some vids on mordant black, napththol green, methyl red, etc..
Great video! Could you explain what is happening in the reaction between methylene blue and a solution of sodium perchlorate? Why does it seem to be reducing it?
I always love watching your videos
Thank you!! 💕
Amazing video!!!!
Thanks!
While a LOT of old medicine was dangerous to completely bunk, sometimes they really did find stuff that worked, but with the inability to identify exactly why, and isolate harmful from helpful, it was rough for sure.
Yep thats absolutely right
Hi, i'm a big fan. I wanted to ask (because your videos always humble me and I question myself if I even know chem.) If I wanted to learn ochem to a level where I could understand and research similar things like you, or solving some problems from Icho without being clueless, where should I start and how do I expand from there speaking from your experience
Hey there! First of all, thanks so much for being a fan and watching my stuff :)
My experience is "unfortunately just academic" - so I went through things over many years and read a bunch of books (eg for total synthesis, Nicolaous series). The time and repetition are really what deepen your understanding. At what point are you at now, which topics in particular do you want to learn more about? I might then give you some more specific suggestions
Btw, I am working on a written exercise book for chemistry that might be helpful for folks like you or students - in the future (its taking me forever as Im over 100 pages). Are there any specidic topics from your experience that are not well explained in school of elsewhere?
@@totalsynthesis hi, thanks for a response, since I have a lot of free time I was planning to relearn ochem because I was introduced to this subject in hs and I liked it, but it missed the point of why and how. So generally
1)I'd like some textbook suggestions to reintroduce me to ochem from beginning again(clayden is often recommended), and after that some "rigorous" ones which I can connect onto that will give me intuition(eg some compound is end result predict compounds A B which are reactants or alike for that reaction). I say rigorous because I don't really know what next step in studying ochem is after getting basics right.
2)I'd also like some problem oriented book in that regard, since im planning to enter hs chem competition and maybe qualify for icho if I sharpen other branches of chemistry too(problems that don't req. calculus).
Thanks for taking time to respond, I appreciate that.
@@badza7247 Clayden is the one I used most so I can also recommend. It's pretty long so it covers the basics well. Another popular one is "Organic Chemistry As a Second Language". More advanced and problem-oriented are are "The Art of Writing Reasonable Organic Reaction Mechanisms" by Grossman and "Organic Synthesis: The Disconnection Approach" by Warren and Wyatt. For understanding the science behind complex synthesis, "The Logic of Chemical Synthesis" by Corey
Someone please help me if BASF is the largest producer (by revenue).
Then why does China export 3x as much?
China: $141.3 billion (18.4% of total chemical exports)
United States: $67.9 billion (8.8%)
Germany: $49.5 billion (6.4%)
Ireland: $48.5 billion (6.3%)
Korea: $40.4 billion (5.2%)
Belgium: $38 billion (4.9%)
Switzerland: $31.8 billion (4.1%)
Netherlands: $31.1 billion (4%)
What is Germany doing with more drugs than China if it is not exporting it? Would they be massing it, or is that by revenue and not the same as actual production? Please clarify, thanks!
Also, would that include Chinas black market fent/ice?
www.statista.com/statistics/272704/top-10-chemical-companies-worldwide-based-on-revenue/
I love the thumbnail
Ahahha thanks!
Random question but how easy is it to Make Palfium aka dextromoramide ?? Btw love your channel!!!
I think relatively easy but highly controlled/illegal
Thanks!!
22:08 “different cycloarsine rings”
Could you say they are…
*_As-holes?_*
Hahaha, sus
Your videos are much more in depth and informative than most of the other creators out there. Liked and subscribed 🤌
Thanks! Appreciate it :)
Gobless🙌🏽😅
Think there is some reference to blue/purple and medicine in greek bible.
You channel is great, just to know, are u from ETH?
I was, yes
Jummy jummy mummy in my tummy!
😂😂😂
chemo therapy is not modern.
True, although still extremely commonly used and I was thinking about modern applications like antibody-drug conjugates (which one of my future videos will be about)
This looks like another LLM-generated video.
Huh?
I have friends that use methylene blue for cognitive effects lol
Really? Wow
I do, but can't tell yet if it's doing anything. I'll keep it up and report back if I have any striking effects.
Mummia / mumiye is not asphalt, it is shilajit. What are you on?
Bitumen resin aka asphaltum
en.m.wikipedia.org/wiki/Mummia
Shilajit, Mumiye and Asphaltos are all somewhat similar in composition - mostly assorted cyclic and acyclic hydrocarbons
Asstastically clAssic
😂
@@totalsynthesisThe symbol for arsenic is the first two letters of the word ass
Coincidence? I think not!
Like this comment
👍
and comment , gang gang
You're right
I should
My grandfather mixed old motor oil with sulfur powder to treat his hunting hounds for skin problems…
Hardcore
@@totalsynthesis Must have worked, or he wouldn’t have done it. He loved those dogs more than mankind, and now I’m starting to feel like that also…lol. I’m an analytical chemist BTW. Maybe he inspired me!